This proposed research involves a long term study of the metabolic effects of the thyroid hormones on cells in culture. A cell culture system has been developed which is sensitive to the physiologic and pathologic concentrations of thyroxine (T4) and triiodothyronine (T3) determined in man. Iodothyronines inactive in animals and man are also inactive in this system. In the cell culture T4 and T3 induce a maximal 3 to 4-fold increase in glucose utilization, oxygen consumption, carbon dioxide production and cell growth. Associated with these findings is an increase in uridine transport and/or phosphorylation which can be demonstrated within several hours after the addition of T4 or T3. The mechanism of action of the thyroid hormones will be studied with regard to the temporal relation of these observations with particular respect to transcriptional and translational control mechanisms. This research will also include a study of the role of specific hormone receptor sites, as well as the necessity of the conversion of T4 to T3 as a requirement for the biologic action of T4. In addition, these changes will be investigated with regard to a possible role of 3', 5': cyclicAMP. It is hoped that these studies will have the dual effect of clarifying the molecular mechanism involved in the action of the thyroid hormones as well as providing basic information concerning the nature of the regulatory mechanisms involved in cell growth.